Periplocin ameliorates mouse age-related meibomian gland dysfunction through up-regulation of Na/K-ATPase via SRC pathway.

Age-related meibomian gland dysfunction (MGD) is the main cause of evaporative dry eye disease in an aging population. Decreased meibocyte cell renewal and lipid synthesis are associated with age-related MGD. Here, we found an obvious decline of Ki67, ΔNp63, and Na+/K+ ATPase expression in aged meibomian glands. Potential Na+/K+ ATPase agonist periplocin, a naturally occurring compound extracted from the traditional herbal medicine cortex periplocae, could promote the proliferation and stem cell activity of meibocyte cells in vitro. Moreover, we observed that periplocin treatment effectively increased the expression of Na+ /K+ ATPase, accompanied with the enhanced expression of Ki67 and ΔNp63 in aged meibomian glands, indicating that periplocin may accelerate meibocyte cell renewal in aged mice. LipidTox staining showed increased lipid accumulation after periplocin treatment in cultured meibomian gland cells and aged meibomian glands. Furthermore, we demonstrated that the SRC pathway was inhibited in aged meibomian glands; however, it was activated by periplocin. Accordingly, the inhibition of the SRC signaling pathway by saracatinib blocked periplocin-induced proliferation and lipid accumulation in meibomian gland cells. In sum, we suggest periplocin-ameliorated meibocyte cell renewal and lipid synthesis in aged meibomian glands via the SRC pathway, which could be a promising candidate for age-related MGD.

Ocular surface changes in the treatment of rosacea: comparison between low-dose oral isotretinoin and doxycycline / Alterações da superfície ocular no tratamento da Rosácea: comparação entre isotretinoína oral em baixa dosagem e doxiciclina

ABSTRACT Purpose: To compare the impact of ocular changes between systemic treatment with doxycycline and low-dose oral isotretinoin in patients with moderate-to-severe papulopustular rosacea. Methods: Patients were randomized to receive either isotretinoin 0.3-0.4 mg/kg (group A) or doxycycline 100 mg/day (group B) for 16 weeks. Ocular symptoms were searched and evaluated, including best-corrected visual acuity (BCVA), Schirmer test, breakup time, rose bengal staining score, and meibomian gland dysfunction grading. The patients were retested at the end of treatment. Results: The present study included 39 patients (30 females and 9 males). Best-corrected visual acuity was > 20/30 in >90% of patients in both groups and did not change after treatment. After treatment, improvement in ocular symptoms and meibomian gland dysfunction was more pronounced in group B (p<0.05); the other parameters did not reach statistical significance. Conclusion: Doxycycline improved meibomian gland dysfunction, ocular symptoms, and ocular surface in patients with rosacea. Even though some patients experienced worsening meibomian gland dysfunction and symptoms, no subject experienced any serious complications after administration of low-dose isotretinoin.

RESUMO Objetivos: Comparar o impacto das alterações oculares entre o tratamento sistêmico de doxiciclina e isotretinoína em baixa dosagem em pacientes com rosácea papulopustulosa moderada a grave. Métodos: Os pacientes form randomizados para receber isotretinoína 0,3 a 0,4 mg/kg (grupo A) ou doxiciclina 100mg/dia (grupo B) por 16 semanas. Os sintomas oculares foram pesquisados e avaliados, incluindo melhor acuidade visual corrigida, teste de Schirmer, tempo de ruptura do filme lacrimal, coloração de rosa bengala e graduação da disfunção de glândula de Meibomius. Os pacientes foram novamente testados no final do tratamento. Resultados: O presente estudo incluiu 39 pacientes (30 mulheres e 9 homens). A melhor acuidade visual corrigida foi >20/30 em >90% dos pacientes em ambos os grupos e não se alterou após o tratamento. A melhora dos sintomas oculares e da disfunção de glândula de Meibomius foi mais pronunciada no grupo B (p<0,05) após o tratamento; as demais variáveis não atingiram significância estatística. Conclusão: A doxiciclina melhorou a disfunção de glândula de Meibomius, os sintomas oculares e a superfície ocular de pa cientes com rosácea. Mesmo que alguns pacientes tenham piorado a disfunção e os sintomas da glândula de Meibomius, nenhum indivíduo apresentou complicações graves após a admi nistração de baixas doses de isotretinoína.

Effectiveness of meibomian gland massage combined with topical levofloxacin against ocular surface flora in patients before penetrating ocular surgery.

OBJECTIVE: To investigate the bacterial profile in the conjunctiva and meibomian glands in patients before penetrating ocular surgeries, and to compare the anti-bacterial efficacy of 0.5% levofloxacin and its combination with meibomian gland massage. DESIGN: Hospital-based, case-control study. PARTICIPANTS: Two hundred and twenty-six eyes from 226 patients with non-infective ocular diseases and scheduled for penetrating ocular surgeries. METHODS: Tested eyes were administered topical 0.5% levofloxacin (4 times daily) for 2 days. Among them, 91 eyes received meibomian gland massage before levofloxacin application. Samples from the conjunctival sac and meibomian glands were collected for aerobic and anaerobic cultures. MAIN OUTCOME MEASURES: Culture-positivity and bacterial strains. RESULTS: Before treatment, aerobes and anaerobes were cultured from 38.5% and 11.0% of the conjunctival samples respectively, compared with 38.5% and 8.8% in the meibomian secretions respectively. Staphylococcus epidermidis and Propionibacterium acnes were the commonest isolated aerobe and anaerobe. Two-day application of levofloxacin reduced aerobic growth to 29.6% in the conjunctiva and 19.3% in the meibomian glands. It had no effect on the anaerobes in these regions (13.3% in the conjunctiva and 10.4% in the meibomian glands). Combined levofloxacin with meibomian gland massage further reduced aerobic growth to 19.8% in the conjunctiva and 11.0% in the meibomian glands. It also drastically decreased anaerobic growth in the meibomian glands (1.1%). CONCLUSIONS: Meibomian glands carrying considerable bacteria should be considered as a potential source of contamination in ocular surgery. Meibomian gland massage shows additional anti-bacterial effects to topical levofloxacin and could be recommended as a complementary preoperative prophylaxis.

In vitro effects of sex hormones in human meibomian gland epithelial cells.

Meibomian gland dysfunction (MGD) is considered the most common cause of dry eye disease (DED). Sex hormones seem to play a role in the pathogenesis of MGD although their involvement is not completely understood. Therefore, in the present study we evaluated the effect of dihydrotestosteron (DHT) and estradiol (ß-Est) on an immortalized human meibomian gland epithelial cell line (HMGEC). Protein expression of sex hormone receptors in HMGEC was investigated by western blot. Ultrastructural morphology, Sudan III lipid staining, cell proliferation as well as vitality assays were performed. Furthermore, expression of MGD-associated markers for keratinization (hornerin, involucrin and CK6), proliferation (CK5 and CK14) and lipid synthesis (fatty acid synthase and stearoyl-CoA desaturase) were analyzed by real time RT-PCR. Western blot revealed presence of androgen receptor (AR), estrogen receptors α and -ß (ERα, ERß) and progesterone receptor (PR) in HMGEC. PR, ERα and ERß expression was significantly induced under cultivation with serum, whereas sex hormones stimulation showed no further effect on protein expression of PR, ERα and ERß. Our results showed no impact of MGD-associated sex hormones to cellular morphology and lipid accumulation in HMGEC. Cell proliferation was slightly induced through application of sex hormones and supplementation of calcium. However, both sex hormones and calcium altered gene expression of MGD-associated markers. Especially keratinization genes hornerin (HRNR) and cornulin (COR) were induced after application of sex hormones and calcium in serum-free cultivated HMGEC. This may promote keratinization processes that are associated with MGD. Further investigations are necessary to analyze the (hyper)keratinization processes that occur during MGD and using HMGEC as an in vitro model.

Effect of Oral Re-esterified Omega-3 Nutritional Supplementation on Dry Eyes.

PURPOSE: To assess the effect of oral re-esterified omega-3 fatty acids on tear osmolarity, matrix metalloproteinase-9 (MMP-9), tear break-up time (TBUT), Ocular Surface Disease Index (OSDI), fluorescein corneal staining, Schirmer score, meibomian gland dysfunction (MGD) stage and omega-3 index in subjects with dry eyes and confirmed MGD. METHODS: This was a multicenter, prospective, interventional, placebo-controlled, double-masked study. Subjects were randomized to receive 4 softgels containing a total of 1680 mg of eicosapentaenoic acid/560 mg of docosahexaenoic acid or a control of 3136 mg of linoleic acid, daily for 12 weeks. Subjects were measured at baseline, week 6, and week 12 for tear osmolarity, TBUT, OSDI, fluorescein corneal staining, and Schirmer test with anesthesia. MMP-9 testing and omega-3 index were done at baseline and at 12 weeks. RESULTS: One hundred five subjects completed the study. They were randomized to omega-3 (n = 54) and control group (n = 51). Statistically significant reduction in tear osmolarity was observed in the omega-3 group versus control group at week 6 (-16.8 ± 2.6 vs. -9.0 ± 2.7 mOsm/L, P = 0.042) and week 12 (-19.4 ± 2.7 vs. -8.3 ± 2.8 mOsm/L, P = 0.004). At 12 weeks, a statistically significant increase in omega-3 index levels (P < 0.001) and TBUT (3.5 ± 0.5 s vs. 1.2 ± 0.5 s, P = 0.002) was also observed. Omega-3 group experienced a significant reduction in MMP-9 positivity versus control group (67.9% vs. 35.0%, P = 0.024) and OSDI scores decreased significantly in omega-3 (-17.0 ± 2.6) versus control group (-5.0 ± 2.7, P = 0.002). CONCLUSIONS: Oral consumption of re-esterified omega-3 fatty acids is associated with statistically significant improvement in tear osmolarity, omega-3 index levels, TBUT, MMP-9, and OSDI symptom scores.

Influence of Omega 3 and 6 Fatty Acids on Human Meibomian Gland Epithelial Cells.

PURPOSE: Oral supplementation with omega 3 (ω-3) and/or 6 (ω-6) fatty acids (FAs) has been reported to alleviate the signs and symptoms of dry eye disease and to improve the expressibility and quality of meibum, in patients with meibomian gland dysfunction. We tested our hypothesis that these FA effects may reflect a direct FA action on human meibomian gland epithelial cells. METHODS: Immortalized human meibomian gland epithelial cells (IHMGECs) were cultured with ω-3, ω-6, or both FAs together for up to 7 days in the presence or absence of serum. After FA exposure, cells were analyzed for lipid expression, lysosome content, and proliferative ability. RESULTS: Our research shows that ω-3 and ω-6 stimulate the accumulation of small neutral lipid-containing vesicles, but not lysosomes, in IHMGECs. This vesicular effect was associated with a 2.4- to 3.7-fold increase in the cellular content of triglycerides after ω-3 and ω-6 treatment, respectively. The combination of both FAs together also enhanced triglyceride levels. Of interest, culture of IHMGECs with ω-3 and azithromycin, a known inducer of IHMGEC differentiation, led to a significantly greater amount of total neutral lipids, relative to that found with azithromycin alone. Cellular exposure to the FAs did not alter the expression of free or esterified cholesterol, or phospholipids. Further, these FAs, alone or together, prevented the proliferation of IHMGECs in serum-free, but not serum-containing, media. CONCLUSIONS: Our findings support our hypothesis and demonstrate that ω-3 and ω-6 can act directly on IHMGECs to influence the quality and quantity of intracellular lipids.

[Demodex folliculorum a hidden cause of blepharitis].

UNLABELLED: Meibomian gland dysfunction (MGD) is a common cause of dry eye disease. Demodex mites can cause MGD with symptoms like itching, dryness and general ocular discomfort. It is important to consider infestation with Demodex mites in individuals who are non responsive to traditional MGD treatment but also equally important when cylindrical dandruff is seen at the base of the eye lashes.. We report two individuals who had not responded to ocular and systemic treatment for MGD and were then diagnosed with Demodex mites. Treatment with BlephEx and Tea tree oil was successful. This is the first report on Demodex folliculorum in Iceland where a genetic analysis was done. KEY WORDS: Demodex, blepharitis, debris, tea tree oil, dry eye. Correspondence: Sigurlaug Guðrún Gunnarsdóttir sigurlaug@sjonlag.is.

Demodex treatment in external ocular disease: the outcomes of a Tasmanian case series.

Demodex species (spp.) have previously been implicated in the pathogenesis of blepharitis. This study aims to correlate improvement in symptoms of external ocular disease with treatment of underlying Demodex spp. This is a prospective, observational case series of patients with chronic external ocular disease. Demodicosis was confirmed by microscopic examination of epilated eyelashes. The main outcome measure was response to the treatment (5 % tee tree oil) in regard to change in subjective symptoms utilising a symptom-based patient questionnaire assessment. Overall patients had a good response to the treatment in terms of improvement or resolution of symptoms, with 91 % of patients reporting at least some improvement in symptoms. The treatment of underlying Demodex spp. appears to result in improvement of symptoms in patients with long standing external ocular disease and underlying Demodex spp. infestation.

In vitro effects of docosahexaenoic and eicosapentaenoic acid on human meibomian gland epithelial cells.

To investigate the effect of ω-3 fatty acids on human meibomian gland epithelial cells (HMGECs, cell line) in vitro. HMGECs were stimulated with docosahexaenoic acid (DHA) or combinations with eicosapentaenoic acid (EPA) and acetyl sialic acid (ASA). Sudan III fat staining, viability and proliferation assays, electric cell-substrate impedance sensing, real-time PCR for gene expression of cyclooxygenase-2 and 15-lipoxygenase and ELISAs for resolvin D1 (RvD1), IFNγ, TNFα and IL-6 were applied. Lipid droplet accumulation and viability was increased by 100 µM DHA in the presence or absence of EPA in serum cultured HMGECs. In contrast, HMGECs cultured with DHA and EPA under serum-free conditions showed minimal lipid accumulation, decreased proliferation and viability. Normalized impedance was significantly reduced in serum-free cultured HMGECs when stimulated with DHA and EPA. HMGECs cultured in serum containing medium showed increased normalized impedance under DHA and EPA stimulation compared to DHA or EPA alone or controls. IL-6 and IFNγ were downregulated in HMGECs treated for 72 h with DHA and EPA. In general, TNFα, IFNγ and IL-6 levels were decreased after 72 h compared to 24 h in serum containing medium with or without DHA or EPA. The concentration of RvD1 was elevated 2-fold after DHA treatment. Cyclooxygenase-2 gene expression decreased compared to controls during DHA stimulation after 72 h. Treatment with DHA and ASA revealed a decreased 15-lipoxygenase gene expression which was reduced after three days of DHA incubation. DHA and EPA supplementation affected HMGECs in vitro and supported anti-inflammatory effects by influencing cytokine levels, decreasing COX-2 expression and increasing the production of RvD1.

Effect of oral omega-3 Fatty Acid supplementation on contrast sensitivity in patients with moderate meibomian gland dysfunction: a prospective placebo-controlled study.

PURPOSE: To evaluate the effect of oral supplementation with omega-3 (ω-3) fatty acids (FAs) in improving contrast sensitivity (CS) of patients with moderate meibomian gland dysfunction (MGD). METHODS: In this prospective study, 60 patients with moderate MGD were allocated alternately to treatment and control groups. Both groups received warm compresses, lid massage, and artificial tear substitutes. The treatment group also received oral supplements of 1.2 g ω-3 FAs per day. All parameters were recorded at baseline and at 12 weeks and included Ocular Surface Disease Index scores, CS testing at 3, 6, 12, and 18 cycles per degree (cpd), tear break-up time, Schirmer test I without anesthesia, corneal and conjunctival staining scores, and meibum quality and expressibility. RESULTS: At the end of 12 weeks, significant improvement in CS was seen in the treatment group in 7 of the 8 testing conditions (3, 6, 12, and 18 cpd photopic and 6, 12, and 18 cpd mesopic), whereas in the placebo group, significant improvement was seen only in 3 of the 8 testing conditions (3 cpd photopic, 6 and 18 cpd mesopic). Ocular Surface Disease Index, tear break-up time, ocular surface staining, and meibum quality and expressibility improved significantly in both groups, but more so in the treatment group. Schirmer scores showed no significant improvement in either group. CONCLUSIONS: Oral supplementation with ω-3 FAs significantly improved CS under both photopic and mesopic testing conditions in patients with moderate MGD. Tear film stability also improved significantly, whereas no effect was seen on aqueous tear production.

A randomized, double-masked study to evaluate the effect of omega-3 fatty acids supplementation in meibomian gland dysfunction.

BACKGROUND: Dysfunction of the meibomian gland (MG) is among the most frequent causes of ophthalmological symptoms. The inflammation seen in meibomian gland dysfunction (MGD) is part of its pathogenesis, and evidence of the antioxidant-inflammatory properties of omega-3 fatty acids suggests this to be an appropriate treatment for MGD. OBJECTIVE: We aimed to assess the effectiveness of omega-3 fatty acids versus placebo, in improving the symptoms and signs of MGD. METHODS: We conducted a randomized and double-mask trial of 3 months duration. We enrolled 61 patients who presented with symptomatic MGD and no tear instability (defined as tear breakup time [TBUT] <10 seconds). Participants were randomly assigned to two homogeneous subgroups. For patients in group A, the study treatment included cleaning the lid margins with neutral baby shampoo and use of artificial tears without preservatives, plus a placebo oral agent. For patients in group B, the study treatment included cleaning the lid margins with neutral baby shampoo and use of artificial tears without preservatives, plus oral supplementation with omega-3 fatty acids. We performed the following tests: (1) TBUT; (2) Schirmer I test; (3) Ocular Surface Disease Index© (OSDI©; Allergan, Inc., Irvine, CA, USA); (4) MG expression; (5) evaluation of lid margin inflammation; and (6) interpalpebral and corneal dye staining. RESULTS: After 3 months of evaluation, the mean OSDI, TBUT, lid margin inflammation, and MG expression presented improvement from the baseline values, in group B (P < 0.01, P < 0.001, P < 0.0001, P < 0.0001, respectively). The Schirmer test results were also improved and statistically significant (P < 0.01). CONCLUSION: Oral omega-3 fatty acids, 1.5 grams per day, may be beneficial in the treatment of MGD, mainly by improving tear stability.

A randomized double-masked study of 0.05% cyclosporine ophthalmic emulsion in the treatment of meibomian gland dysfunction.

PURPOSE: To compare the efficacy of topical cyclosporine [0.05% cyclosporine A (CsA)] and preservative-free artificial tears in the treatment of meibomian gland dysfunction (MGD). METHODS: A 3-month prospective, randomized, double-masked, parallel-group controlled trial enrolled 70 patients with symptomatic MGD and unstable tear film [tear breakup time (TBUT) <8 seconds]. Patients were randomized to topical CsA (0.05%; group A) and 0.5% carboxymethylcellulose (control; group B) instilled twice daily for 3 months. Ocular Surface Disease Index (OSDI), lid margin inflammation, meibomian gland expression, conjunctival injection, corneal and interpalpebral dye staining, noninvasive tear breakup time (NIBUT) using the Tearscope Plus and invasive fluorescein tear breakup time (FBUT), and Schirmer I test were performed. RESULTS: At the 3-month evaluation, mean OSDI, NIBUT and FBUT, lid margin inflammation, meibomian gland expressibility, and tarsal injection showed significant improvement from baseline in group A (P<0.01, P<0.01, P<0.001, P<0.05, and P<0.001, respectively). In group B, only the OSDI improved significantly from baseline at 3 months (P=0.003). TBUTs (NIBUT and FBUT) were significantly longer in group A at all visits, and the mean change of TBUTs from baseline was also significantly greater in group A at 3 months (P<0.001). CONCLUSIONS: Topical CsA 0.05% twice daily may be helpful in the treatment of MGD mainly by improving tear film stability.

[Meibomian gland dysfunction]. / Meibom-Drüsen-Dysfunktion.

Meibomian gland dysfunction (MGD) is a chronic disease, usually caused by obstruction of the secretory Meibomian glands. The subsequent reduction of gland secretion results in a decreased amount of lipids in the tear film. This results in a faster evaporation of the tear film and thus an evaporative dry eye. MGD alone is responsible for about 60% of all cases in combination with aqueous deficiency for a further 20% of dry eyes. While in Europe up to 20% of the population are suffering from MDD, this is true in Asia for over 60% of the population. MGD is more common in women and it incidence increases with age. It is influenced by the hormonal status as well as chemical and mechanical noxious stimuli. Additional risk factors include various skin diseases such as rosacea, acne or atopy. To diagnose MGD, particular attention should be paid to changes in the lid margin such as plugging or pouting of the ducts, thickening and telangiectasia. However, most important is the diagnostic expression of the glands. At first it should be assessed whether secretion can be caused by pressure to the eyelid against the globe and secondly the quality of the expressed secretions should be evaluated. MGD should be treated according to the severity of the disease. While in mild stages instructions for lid margin hygiene, warming and massage in combination with artificial tears might be sufficient, in more severe stages oral tetracyclin derivatives and anti-inflammatory eye drops such as steroids or CSA are necessary for successful treatment.

Pilot, prospective, randomized, double-masked, placebo-controlled clinical trial of an omega-3 supplement for dry eye.

PURPOSE: To investigate the potential effect of dietary supplementation with omega-3 fatty acid on lipid composition of meibum, aqueous tear evaporation, and tear volume in patients with dry eye. METHODS: In a pilot, prospective, randomized, double-masked study, patients with dry eye received a daily dose of fish oil, containing 450 mg of eicosapentaenoic acid, 300 mg of docosahexaenoic acid, and 1000 mg of flaxseed oil (TheraTears Nutrition; Advanced Vision Research, Woburn, MA) for 90 days. There were 2 patient visits: baseline and final. At these visits, patients completed the ocular surface disease index to score subjective symptoms, and slit-lamp examinations, breakup time, corneal staining, Schirmer type I, fluorophotometry, evaporometry, and collection of meibomian gland secretion samples for lipid composition analysis were performed. RESULTS: A total of 36 patients with dry eye completed the study. At the end of the study, 70% of the patients became asymptomatic, whereas for the placebo group, 37% [corrected] of the symptomatic patients became asymptomatic. Schirmer testing and fluorophotometry suggested that the omega-3 supplement increased tear secretion. The lipid composition of the samples collected from the omega-3 group was found to be very similar to that from the placebo group. No trends between groups were seen for other objective parameters. CONCLUSIONS: Dietary supplementation with omega-3 fatty acids in dry eye showed no significant effect in meibum lipid composition or aqueous tear evaporation rate. On the other hand, the average tear production and tear volume was increased in the omega-3 group as indicated by both Schirmer testing and fluorophotometry.

The role of omega-3 dietary supplementation in blepharitis and meibomian gland dysfunction (an AOS thesis).

PURPOSE: Blepharitis and meibomian gland dysfunction (MGD) are common sources of complaints from patients. To evaluate the effect on ocular symptoms, ocular findings, and serum and meibomian gland contents, patients with blepharitis and MGD were prospectively evaluated to determine the effects of dietary supplementation with omega-3 fatty acids. METHODS: In a prospective randomized placebo-controlled masked trial, patients with simple obstructive MGD and blepharitis, who had discontinued all topical medications and tetracyclines, received oral omega-3 dietary supplementation consisting of two 1000-mg capsules 3 times a day. Patients were examined every 3 months for 1 year with the Ocular Surface Disease Index (OSDI) objective clinical measures, including tear production and stability, ocular surface and meibomian gland health, and biochemical plasma, red blood cell (RBC), and meibum evaluation. Primary outcome measures were change in tear breakup time (TBUT), meibum score, and overall OSDI score at 1 year. RESULTS: At 1 year, the omega-3 group had a 36% and 31% reduction in their omega-6 to omega-3 fatty acid ratios in RBCs and plasma, respectively (P = .3), whereas the placebo group demonstrated no change. At 12 months, the omega-3 group had an improvement in TBUT, OSDI score, and meibum score. Changes in meibum content were observed in the omega-3 group (P = .21); the level of meibum saturated fatty acids decreased. CONCLUSIONS: This trial demonstrated a decrease in the RBC and plasma ratios of omega-6 to omega-3 in patients taking omega-3 dietary supplementation, as compared to controls, and improvements in their overall OSDI score, TBUT, and meibum score. This is the first demonstration of an induced change in the fatty acid saturation content in meibum as a result of dietary supplementation with omega-3 fatty acids.

The effect of low-dose doxycycline therapy in chronic meibomian gland dysfunction.

PURPOSE: The aim was to investigate the effect of low dose doxycycline (20 mg) therapy in patients with chronic meibomian gland dysfunction that were refractory to conventional therapy. METHODS: The randomized prospective study enrolled 150 patients (300 eyes) who have chronic meibomian gland dysfunction and who didn't respond to lid hygiene and topical therapy for more than 2 months. All topical therapy was stopped for at least 2 weeks prior to beginning the study. After conducting the tear break up time test (TBUT) and Schirmer test, the authors randomly divided the patients into three groups a high dose group (doxycycline, 200 mg, twice a day), a low dose group (doxycycline, 20 mg, twice a day) and a control group (placebo). After one month, the author repeated the TBUT and Schirmer tests, and analyzed the degree of symptomatic improvement. RESULTS: Compared to the control group, both the high and low dose group showed statistically significant differences after treatment in TBUT, Schirmer test, the number of symptoms reported and the degree of improvement of subjective symptoms. However, there was no statistically significant difference between the high and low dose group after treatment in TBUT (9.42 +/- 2.87 sec, 9.54 +/- 1.58 sec, p=0.726), Schirmer test (19.98 +/- 4.05 mm, 19.65 +/- 5.02 mm, p=0.624), the number of symptoms reported (1.45 +/- 0.62, 1.53 +/- 0.52, p=0.304), as well as the degree of improvement of subjective symptoms (p=0.288). The high dose group (18 patients, 39.13%) reported side effects more frequently than did the low dose group (8 patients, 17.39%) (P=0.002). CONCLUSIONS: Low dose doxycycline (20 mg twice a day) therapy was effective in patients with chronic meibomian gland dysfunction that were refractory to conventional therapy.

The Effect of Low-Dose Doxycycline Therapy in Chronic Meibomian Gland Dysfunction

PURPOSE: The aim was to investigate the effect of low dose doxycycline (20 mg) therapy in patients with chronic meibomian gland dysfunction that were refractory to conventional therapy. METHODS: The randomized prospective study enrolled 150 patients (300 eyes) who have chronic meibomian gland dysfunction and who didn't respond to lid hygiene and topical therapy for more than 2 months. All topical therapy was stopped for at least 2 weeks prior to beginning the study. After conducting the tear break up time test (TBUT) and Schirmer test, the authors randomly divided the patients into three groups a high dose group (doxycycline, 200 mg, twice a day), a low dose group (doxycycline, 20 mg, twice a day) and a control group (placebo). After one month, the author repeated the TBUT and Schirmer tests, and analyzed the degree of symptomatic improvement. RESULTS: Compared to the control group, both the high and low dose group showed statistically significant differences after treatment in TBUT, Schirmer test, the number of symptoms reported and the degree of improvement of subjective symptoms. However, there was no statistically significant difference between the high and low dose group after treatment in TBUT (9.42+/-2.87 sec, 9.54+/-1.58 sec, p=0.726), Schirmer test (19.98+/-4.05 mm, 19.65+/-5.02 mm, p=0.624), the number of symptoms reported (1.45+/-0.62, 1.53+/-0.52, p=0.304), as well as the degree of improvement of subjective symptoms (p=0.288). The high dose group (18 patients, 39.13%) reported side effects more frequently than did the low dose group (8 patients, 17.39%) (P=0.002). CONCLUSIONS: Low dose doxycycline (20 mg twice a day) therapy was effective in patients with chronic meibomian gland dysfunction that were refractory to conventional therapy.

Quantification of tear interference image: tear fluid surface nanotechnology.

PURPOSE: To review the literature on lipid supplementation therapy for dry eye and on image analysis using tear interference images from the specific tear lipid layer interference camera DR-1. METHODS: Systematic literature review of lipid supplementation therapy for lipid tear deficiency dry eye, kinetic analysis of tear interference images using DR-1 camera, and computer-synthesized interference color chart for DR-1 camera. CONCLUSION: To establish lipid supplementation therapy, a quantification system of tear lipid layer is required. Tear lipid thickness could be quantified using a computer-synthesized interference color chart system.

Low-concentration homogenized castor oil eye drops for noninflamed obstructive meibomian gland dysfunction.

OBJECTIVE: We developed low-concentration homogenized castor oil eye drops for the treatment of patients with noninflamed obstructive meibomian gland dysfunction (MGD), a major cause of lipid-deficiency dry eye, and assessed the safety, stability, and efficacy of the eye drops. DESIGN: Randomized, double-masked, placebo-controlled crossover clinical trial. PARTICIPANTS: Forty eyes of 20 patients with noninflamed MGD. METHODS: After a preliminary study of eye drops containing castor oil, 2% castor oil and 5% polyoxyethylene castor oil (emulsifier) were mixed to formulate homogenized oil eye drops. The patients were assigned randomly to receive oil eye drops or placebo six times daily for 2 periods of 2 weeks each. MAIN OUTCOME MEASURES: At the end of each treatment period, we assessed symptoms, tear interference grade, tear evaporation, fluorescein and rose bengal scores, tear break-up time (BUT), and meibomian gland orifice obstruction. Safety and stability tests were also performed. RESULTS: Symptom scores, tear interference grade, tear evaporation test results, rose bengal scores, tear BUT, and orifice obstruction scores after the oil eye drop period showed significant improvement compared with the results after the placebo period. No complications attributable to the eye drops were observed. The oil eye drops were stable when stored at 4 degrees C. CONCLUSIONS: The results indicate that castor oil eye drops are effective and safe in the treatment of MGD. The possible mechanisms of this treatment are improvement of tear stability as a result of lipid spreading, ease of meibum expression, prevention of tear evaporation, and the lubricating effect of the oil eye drops.

Effects of 13-cis-retinoic acid on the hamster meibomian gland.

Systemic administration of 13-cis-retinoic acid caused a reduction of acinar tissue in the hamster meibomian gland. Histologic examination of treated meibomian gland tissue revealed a thickening of gland ductal epithelium and a decrease in the numbers of mature lipid-laden acinar cells. Morphometric analysis showed a reduction of up to 75% in mean volume of meibomian acinar tissue from animals fed a high dose of 13-cis-retinoic acid. Clinical observations in these animals included alopecia and weight loss. Ocular complications included crusting of the eyelid margin and the external surface of the lid and erythema of the conjunctiva. The model supports previous observations by the authors that systemic 13-cis-retinoic acid affects meibomian gland structure in a laboratory animal. The ocular side effects described in this model suggest that future functional studies may yield important insights into the complex relationship between meibomian gland morphology and function, and events on the ocular surface.